The basic aim of our project is to investigate the biochemistry of the ovarian steroidal hormones in regulating the hypothalamic-ovarian axis (particularly progesterone and its 5 alpha-reduced metabolites - 5 alpha-dihydroprogesterone and 3 alpha-hydroxy-5 alpha-pregnan-20-one). We hope to elucidate some of the biochemical regulatory mechanisms involved in these steroid feedbacks at neural and pituitary levels. The information gained is expected to give new insights into the steroidal regulatory mechanism(s) affecting the hypothalamic-ovarian axis, which may ultimately reveal new avenues for fertility regulation. This past year and presently our group has explored such aspects as: 1. The role and properties of the hypothalamic and pituitary metabolizing enzymes of progesterone and 20 alpha-dihydroprogesterone (20 alpha-DHP). 2. The tissue localizatiin of progesterone, 20 alpha-DHP, 5 alpha-dihydroprogesterone and their metabolites after injections of the H3-compounds. We determined the nature and concentration of the H3-steroidal compounds found in a number of neuroendocrine tissues and some of the factors influencing uptake and metabolism. 3. The biologic role of the neuroendocrine metabolites of progesterone. 4. The subcellular localization of the gonadotropin releasing factor(s) with the objective of elucidating the hypothalamic subcellular components involved in the production, storage and release of the gonadotropin releasing factor(s). The above studies should provide the basis for subsequent experiments to elucidate the sequential scheme of molecular events from sex steroid feedback - uptake of steroid reacting molecular species to the ultimate release or inhibition of release of the gonadotropins. BIBLIOGRAPHIC REFERENCES: Nuti, L. C., B. C. Wentworth, H. J. Karavolas, W. J. Tyler, and O. J. Ginther. 1975. Comparison of radioimmunoassay and gas-liquid chromatography analyses of progesterone concentrations in cow's milk. Proc. Soc. Exp. Biol. Med. 149:877-880. Karavolas, H. J., D. Hodges, and D. O'Brien. 1976. Uptake of H3-progesterone and H3-5 alpha-dihydroprogesterone by rat tissues in vivo and analysis of accumulated radioactivity: Accumulation of 5 alpha-dihydroprogesterone by pituitary and hypothalamic tissues. Endocrinology 98:164-1775.